{
  "abstract": "Mitochondria are recognized as pivotal regulators in cell fate determination, and their dysfunction is implicated in numerous major diseases. While mitochondria control classical programmed cell death pathways, including apoptosis, necroptosis, and pyroptosis, the recent identification of mitoxyperiosis, a BAX/BAK1/BID-dependent and spatially restricted mode of oxidative death, has added complexity to this regulatory framework. Nonetheless, a systematic understanding of how mitochondria coordinate these diverse pathways, particularly the mechanistic relationship between canonical death pathways and this newly identified mode, remains insufficiently explored. In this review, we address three fundamental questions: (1) Through which key molecular mechanisms, including mitochondrial outer membrane permeabilization, reactive oxygen species bursts, mitochondrial DNA release, and alterations in mitochondrial dynamics, do mitochondria regulate each major death pathway? (2) How does mitoxyperiosis diverge from and intersect with classical ferroptosis and other death modalities, and what unique features characterize its execution? (3) What therapeutic opportunities and challenges emerge from targeting mitochondrial death checkpoints to protect cells in pathological conditions and to treat cancer? By critically integrating current evidence, we propose a comprehensive framework that elucidates the regulatory logic of mitochondria-mediated cell death and underscores mitochondrial plasticity as a crucial determinant of cellular outcomes. This perspective not only clarifies the integrative role of mitochondria within the cell death network but also suggests new avenues for developing precision therapies for diseases associated with mitochondrial dysfunction.",
  "abstract_shown": true,
  "affiliations": [
    "Intensive Care Unit, Wanbei Coal Electric Group General Hospital, Suzhou, Anhui 234000 China",
    "Central Laboratory, Wanbei Coal Electric Group General Hospital, Suzhou, Anhui 234000 China",
    "Department of Radiology, Suzhou Hospital of Anhui Medical University, Suzhou, Anhui 234000 China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jianxiong Xiao"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuaiyong Qi"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuzhen Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yafen Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Heng Tang",
      "orcid": "0000-0001-8171-5304"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e0skkvs4pvk6j.bib",
  "cited_by": 0,
  "doi": "10.1186/s12967-026-08823-6",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715107/",
  "id": "e0skkvs4pvk6j",
  "issns": [
    "1479-5876"
  ],
  "landing_url": "https://doi.org/10.1186/s12967-026-08823-6",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "1312|Cell death mechanisms and regulation"
    ]
  ],
  "openalex": "W7202356209",
  "pdf_url": null,
  "pmcid": "PMC13715107",
  "pmid": "42947142",
  "published": "2026-08-13",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/e0skkvs4pvk6j.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:29Z",
      "native_id": "PMC13715107",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12967-026-08823-6"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Cell death mechanisms and regulation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mitochondria as the core regulator of cell death: from classical programmed cell death to the novel mitoxyperiosis pathway",
  "title_text": "Mitochondria as the core regulator of cell death: from classical programmed cell death to the novel mitoxyperiosis pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:29Z",
  "url": "https://research.draconitic.com/paper/e0skkvs4pvk6j",
  "venue": "Journal of Translational Medicine",
  "versions": []
}